Urinary extracellular vesicles: does cargo reflect tissue?

Purpose of review To review recent developments in urinary extracellular vesicles (uEVs) to study kidney physiology and disease. Recent findings Proteomic analysis in rats showed significant correlations between kidney and uEV protein abundances. Consistent with uEV biogenesis, these correlations were stronger for membrane-associated proteins than for e.g. soluble kinases or E3 ubiquitin ligases. When challenged with a high potassium diet, the physiologically predicted protein changes occurred both in kidney and uEVs, suggesting that analysis of uEVs might be utilized as a proxy or even replacement for tissue analysis. Although kidney-uEV correlations are more difficult to obtain in humans, analysis of uEV cargo from patients with inherited tubulopathies or with primary aldosteronism were also consistent with the predicted changes at the tissue level. The kidney appears to be the main source of uEVs, with a recent study showing that nephron mass determines uEV excretion rate. Therefore, a measure of nephron mass should be included for between-subject comparisons. The overall good correlation between kidney and uEV protein abundances renders uEVs an attractive noninvasive source of biomarkers for studying kidney physiology or disease. However, differences in per-protein kidney-uEV correlations and per-person uEV excretion rates should be considered in uEV biomarker studies.

Automated summary

This review discusses recent developments in the use of urinary extracellular vesicles (uEVs) for studying kidney physiology and disease. Studies in rats have shown significant correlations between protein levels in the kidney and uEVs, particularly for membrane-associated proteins. Similar protein changes have been observed in both kidney tissue and uEVs when rats are fed a high potassium diet, suggesting that uEVs can be used as a proxy for tissue analysis. While obtaining kidney-uEV correlations in humans is more challenging, analysis of uEVs from patients with kidney disorders has also shown consistent changes. Nephron mass has been identified as the main determinant of uEV excretion rate. Overall, uEVs show promise as noninvasive biomarkers for studying kidney physiology or disease, but the variations in per-protein correlations and per-person excretion rates should be considered in biomarker studies.